Our objective in this Phase II study is to discover a number of novel iron chelators which are suitable candidates for development as an orally available drug. These candidates will be further evaluated in Phase III for filing of an IND and subsequent clinical studies. In Phase I, we established the feasibility of using solid phase combinatorial chemistry for the production of iron chelator libraries and developed method for screening them for iron affinity. In this study we will implement high throughput synthesis and screening in order to identify compounds having high affinity, favorable hydrophobicity, and efficacy in removing iron from cultured hepatocytes. Novel chelators with desirable profiles in preliminary screens will be evaluated in vivo for efficacy and toxicity. PROPOSED COMMERCIAL APPLICATIONS: Diseases associated with excess accumulations of iron include hereditary hemochromatosis, thalassemia and sickle cell anemia (iron overload induced by transfusions). At present the drug of choice is deferoxamine, which must be administered by injection, has a short half-life, and is known to have toxic side effects. These studies will identify candidate compounds which are orally available iron chelators to be taken into clinical studies for development as new drugs.